The endometrium and gynaecological symptoms

Abstract

The sixty-five publications, which are included in this thesis, report a continuous research interest and activity over more than 25 years in the unique and still mysterious process of menstruation, its related symptoms and the various roles of the endometrium in these processes. These research activities are largely a continuation of interests developed during work for my MD thesis. None of the publications submitted for this thesis formed a part of my MD or other thesis.The publications cover three main areas of research: heavy menstrual bleeding; breakthrough bleeding in women using long-acting progestogen-only methods of contraception; and pelvic pain and its relationship to pelvic innervation and local cellular immunology in endometriosis. I have summarised the work presented in the 65 publications in the Introduction, below, with reference to each publication as part of a developing theme, rather than on a chronological basisHEAVY MENSTRUAL BLEEDING (HMB): This section includes 25 papers, beginning with reports of studies aimed at addressing the objective measurement of menstrual blood loss and total fluid loss in different clinical situations where HMB is a problem. These are followed by a series of reports exploring the endometrial vascular and molecular mechanisms of HMB, and further reports addressing the impact of different therapies on abnormal uterine bleeding (AUB). The section culminates with a description of a major effort to develop international agreement on a series of logical terminologies and definitions around normal and abnormal uterine bleeding.BREAK-THROUGH BLEEDING (BTB) WITH LONG-ACTING HORMONAL CONTRACEPTIVES: This section covers 19 papers, beginning with scholarly reviews of early research needs in hormonal contraceptive-induced abnormal vaginal bleeding, followed by the objective assessment of bleeding and bleeding patterns in users of these methods. These are followed by a series of in vivo and in vitro studies of mechanisms of BTB, and three reviews of our changing perspectives on the causes and management of BTB. The section concludes with descriptions of two randomised, double-blind and placebo controlled trials of several potential therapies for BTB.PELVIC PAIN, NERVE FIBRES AND IMMUNE CELLS IN ENDOMETRIOSIS: This section includes 21 papers, which begin with two brief and early attempts to measure relevant cytokine levels in peritoneal fluid and blood in women with endometriosis, leading to a series of novel immuno-histochemical studies of nerve fibres in the eutopic endometrium and ectopic endometriotic lesions. These led us on to the study of local cellular immunology in eutopic endometrium and ectopic lesions, probably with relationships to the pain and nerve fibres. Diagnostic and therapeutic studies are followed by three scholarly reviews of the microanatomy and function of the eutopic endometrium and the relationships to pelvic pain in endometriosis.